The Kenai River is the most popular sport fishing destination in Alaska. Each year there are two runs each of king salmon, silver salmon, red salmon, plus a run of pink salmon every other year. The world record king salmon, which weighed about 44 kg (97 lb), was caught in the Kenai River in 1985. The Kenai is also the home of trophy size rainbow trout and Dolly Varden. Stretching to sizes over 76.2cm (30 inches). Fall fishing is very exceptional for fishing of Rainbow Trout and Dolly Varden. Occasionally there will be reports of catching of "Steelhead"(Sea-run Trout).

The king salmon fishery is not as prolific as in other Alaskan rivers, but the Kenai is known for its large fish. A typical king in the second run, beginning in mid-July, weighs 40–50 pounds (18–23 kg), with considerably larger specimens not uncommon. The "Lower Kenai" is notorious for its run and sizes of its king salmon.

The silver salmon runs occur in early August and late September. The September run is favored by local anglers due to the larger size of the silver salmon.

The red salmon runs are in mid-June (bluebacks) and mid-July. Reds are considered the premier salmon for eating, canning, and smoking.

The pink salmon run occurs in even numbered years only. These fish are considered pests by many anglers because they interfere with catching other species and because, by the time they reach inland freshwater, their meat may be soft and oily compared to other species. Nevertheless, using super-light tackle (e.g., 4-pound test), angling for pinks can be a real treat. On a heavy day, even a casual fisher might catch several dozen of the species.

Along with Kenai's fish, the Kenai River area is home to other wildlife, including moose, bears, and multiple species of birds. In the spring, Beluga whales will travel as far as a mile upstream from the mouth of the river to feed on schools of spawning Hooligan fish.